Sickle cell disease is the most common hemoglobinopathy in the world, and, in the United States, affects approximately 1 in 360 African Americans and 1 in 1200 Latinos. Small vessel occlusion, or vaso-occlusion, is the primary pathology leading to clinical complications of this disease. The most frequent manifestation of vaso-occlusion is the acute pain episode (crisis), which often requires hospitalization and narcotic use, thus exacting an economic, social, and psychological toll on afflicted individuals. Standard of care is inadequate, there being no specific therapies that target ongoing acute pain episodes. Mouse models have shown that leukocytes adherent to blood vessel endothelium play a crucial role in vaso-occlusion, probably through their subsequent interaction with sickle red blood cells. Further work has shown that intravenous lVlG administered either prior to or after the induction of vaso-occlusion rapidly and dramatically reduces leukocyte adhesion to endothelium and subsequent red cell interactions, leading to a marked increase in survival. Based on this work, the investigators propose to conduct a randomized, double-blind, placebo-controlled, dose-escalation Phase 1/2 trial to study the safety and efficacy of a single dose of IVIG compared to normal saline placebo administered to patients with SCD admitted to the hospital with an uncomplicated acute pain episode. A total of 52 subjects will be enrolled. The investigators hypothesize that IVIG will act quickly to reduce vaso-occlusion and thus pain scores, narcotic use, and length of hospitalization. They will also investigate the physiological effects of IVIG in patients with SCD by measuring the adhesion receptors involved in leukocyte adherence to endothelium and red blood cell-leukocyte interactions, microcirculatory blood flow, and serum markers of hemolysis. The investigators expect that completion of this trial will allow them to submit by the end of the grant period a National Institutes of Health application to expand this trial into a Phase 3 trial or to test, in Phase 1/2 trials, newly identified agents that interfere with the molecular mechanism of vaso-occlusion.